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Background & Aims: To investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC), and to identify predictors of complete pathologic response (CPR)., Methods: Between 1990 and 2010, 373 consecutive cirrhotic patients with HCC were treated by TACE followed by either liver resection (LR:184 patients) or liver transplantation (LT:189 patients). The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. CPR was defined as the absence of any viable tumor area in all the present nodules., Results: A total of 59 (32%) and 37 (20%) patients had CPR after LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR compared to those without, after LR (58% vs. 34%; p=0.0006) and tends to be higher after LT (84% vs. 65%; p=0.09). The 5-year recurrence-free survival (RFS) rates were significantly higher in both groups (24% vs. 13% after LR; p=0.008 and 94% vs. 73% after LT, p=0.007). A cut-off value of >90% necrosis emerged as an impacting factor on patient survival after LR or LT. On multivariate analysis stratified on the type of procedure (LR or LT), PR >90% remained an independent factor of better OS and RFS. Independent factors associated with CPR were: a maximal tumor size <30 mm (RR 2.17 [1.27-3.74]), a single tumor (RR 6.08 [3.29-12.07]), and an preoperative AFP<100 ng/ml (see results section) (RR 3.99 [1.63-11.98]). The probability to achieve a CPR ranged from 2% in the absence of any factors to 48% in the presence of all factors., Conclusion: In cirrhotic patients with HCC, a complete or nearly complete PR improves long-term survival after LR and LT independently of other pathological factors. This underlines the importance of neoadjuvant treatment to obtain a significant decrease of active tumor load., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background/aims: As life expectancy in HIV-HCV co-infected patients improves, end stage liver disease requiring liver transplantation (LT) may become an emerging problem. We report the Paul Brousse Hospital experience of transplantation for end stage cirrhosis in HIV-HCV co-infected patients., Methods: Seven consecutive HIV-HCV co-infected patients were transplanted between December 1999 and December 2002 for end stage liver disease due to HCV. All patients were treated by highly active antiretroviral therapy (HAART), HIV plasma viral load was <400 copies/ml and median CD4 lymphocyte count was 306 cells/mm3 (range, 103-510) before LT. At the time of evaluation (March 2003), the median follow-up was 21 months (range, 4-40)., Results: Two patients died, 4 and 22 months, respectively after LT. At the last biopsy, METAVIR score was staged F4 in two patients, F3 in two, and F1 in one. Microvesicular steatosis was noted in nearly all patients. The ratio of mitochondrial to nuclear DNA was low in three of four patients examined as compared with the amount of liver mtDNA found in eight HIV-negative, HCV-infected controls (P=0.01)., Conclusions: A significant defect in the activity of the respiratory chain complex IV was noted in all five patients studied. Mitochondrial hepatotoxicity and severe HCV recurrence occur in HIV-HCV co-infected patients after LT.

Background/aims: Factors influencing the long-term histological outcome of liver graft are not known. We conducted a prospective study based on a 10-year liver biopsy in order to identify the main factors influencing long-term graft histology., Methods: 270 of 423 patients who still had their first functional graft 10 years after liver transplantation accepted to undergo routine liver biopsy. All slides were blindly reviewed by two pathologists., Results: Main histological findings were fibrosis in 143 patients (54%) and ductopenia in 76 patients (29%). Ductopenia was independently related to higher donor age (32+/-12 vs 28+/-13 years; P<0.02). Severity of fibrosis was influenced by hepatitis C virus (HCV) infection (P<0.001), hepatitis B virus (HBV) recurrence (P=0.001) and higher donor age (P=0.03). Eighty biopsies (30%) showed minimal-change lesions which were associated with the absence of HCV infection (24/80 vs 99/185; P<0.001) or of HBV infection (1/80 vs 15/185; P=0.03) and lower donor age (25+/-11 vs 31+/-13 years; P<0.001)., Conclusions: Post-transplant infection by HCV or HBV are main factors influencing the histological course of liver graft. Donor age was also a strong factor in HCV infected patients as well as in HCV-negative patients. This variable should be taken into account, particularly for candidate recipients with long life expectancy.

Background/aims: The place of transjugular intrahepatic porto-systemic shunt (TIPS) for variceal haemorrhage uncontrolled by sclerotherapy and medical treatment is still undefined. To investigate the outcome of early salvage TIPS for active uncontrolled variceal haemorrhage, and to identify the factors associated with mortality., Methods: Salvage TIPS was performed in 58 patients as soon as possible after the diagnosis of variceal bleeding refractory to the combination of sclerotherapy and of pharmacological therapy. Twenty-three variables were assessed prospectively to identify predictors of mortality within 60 days of the procedure., Results: The haemorrhage was controlled in 52 of 58 patients (90%). Bleeding persisted in six of 58 patients (10%), and recurred in four patients (7%). Overall, 17 (29%) and 20 (35%) patients died within respectively 30 days and 60 days of TIPS: five patients died of persistent bleeding, two patients died of recurrent bleeding, and 13 patients died of terminal liver failure. The actuarial survival following salvage TIPS was 51.7% at 1 year. On multivariate analysis, independent predictors of early mortality were: the presence of sepsis (P=0.001), the use of catecholamines for systemic hemodynamic impairment (P=0.009), and the use of balloon tamponade (P=0.04). Neither a single factor, nor a combination of factors before TIPS allowed to predict mortality confidently in a given patient., Conclusions: Early salvage TIPS is an effective treatment to stop active variceal bleeding refractory to sclerotherapy and pharmacological treatment. Pre-treatment prognostic determinants that correlate to mortality can not be used to predict the outcome in individual cases.

The transformation of liver and biliary tract surgery into a full speciality began with the application of functional anatomy to segmental surgery in the 1950's, reinforced by ultrasound and new imaging techniques. The spectrum of gall-stone disease encountered by the hepatobiliary surgeon has changed with the laparoscopic approach to cholecystectomy. There is increased need for conservation techniques to repair the bile duct injuries that arise more often in the laparoscopic approach to cholecystectomy. These and other surgical interventions on the bile ducts should be selected as a function of risk versus benefit in relation to the patient's requirements and the institutional expertise. Bile duct cancers, including hilar cholangiocarcinoma, and gallbladder cancers have a dismal reputation, but evidence is accumulating for better survivals from aggressive approaches performed by specialist hepatobiliary surgeons. Hepatic surgery has increased in safety and effectiveness, largely due to the segmental approach, but also to experience with techniques for vascular control and exclusion used in liver transplantation. Techniques such as portal vein embolisation, which induces hypertrophy of the future remnant liver, percutaneous local tumour destruction using cryotherapy or radiofrequency tumour coagulation and more effective chemotherapy are beginning to increase the number of patients who can undergo curative resection. In liver transplantation, segmental surgery has been applied to graft reduction and to split liver grafts, and is opening new perspectives for living donor transplantation. Today the limitation to survival in primary and metastatic liver cancer lies not in the surgical technique but in the difficulty of dealing with microscopic and extrahepatic disease. Progress in these fields will enable the hepatobiliary surgeon to further extend the possibilities for proposing curative resections.

Background/aims: Hepatitis B virus (HBV) disease on a liver graft is associated with florid viral replication and graft failure. The aim of this study performed between 1992 and 1995 was to investigate the safety and efficacy of long-term intravenous ganciclovir for HBV infection in liver transplant recipients., Methods: Twelve patients with HBV re-infection and four with de novo HBV infection were studied. HBV DNA was positive in all (median titer: 437.5 pg/ml) and HBeAg was positive in seven. Intravenous ganciclovir was started after a median of 14.5 months from HBsAg positivation and continued for a median of 10 months., Results: A complete response with HBV DNA negativation was seen in ten cases, a partial response with a decrease of more than 50% of initial HBV DNA levels in four and no response in two. Overall tolerance was good. Among the ten complete responders, two seroconverted for both HBsAg and HBeAg and one for HBsAg alone. Among these ten patients, three were re-transplanted for liver failure: two of them are alive; three had a viral breakthrough during treatment; and four remained HBV DNA negative: two are alive and two died. Partial responders and nonresponders were treated with other antiviral agents and three were re-transplanted, two of them are alive. Overall 12 out of 16 patients (75%) survived with a median follow up of 46 months., Conclusions: Long-term intravenous ganciclovir can persistently inhibit HBV DNA replication in liver transplant recipients and is well tolerated. Further evaluation should be encouraged, especially for HBV recurrence after first-line treatments.

Background/aims: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown., Methods: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years)., Results: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well., Conclusions: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.

Background/aims: The aim of this study was to clarify the aetiology of apparent de novo HBV infection after liver transplantation., Methods: Twenty out of 570 HBsAg negative patients (3.5%) became HBsAg positive after transplantation and were studied. Donor and recipient sera were retrospectively tested for HBsAg, anti-HBs, anti-HBc, and HBV DNA by PCR. Donor and recipient livers were tested for HBV DNA by PCR on paraffin-embedded tissue., Results: Group 1: HBV infection of donor origin (eight patients): one donor serum was HBsAg positive, three were serum HBV DNA positive, four were liver HBV DNA positive. Group 2: reactivation of latent HBV infection (eight patients) with detection of HBV DNA in pretransplant serum (seven patients) or in native liver (one patient): three were anti-HBs positive, two anti-HBc positive, and three with fulminant hepatitis had no serological HBV markers. Group 3: undetermined origin (four patients) defined by absence of HBV DNA in pretransplant donor and/or recipient sera and liver; however, acquired infection was suspected from two anti-HBs and anti-HBc positive donors. Two patients became HBsAg negative, and five HBV DNA negative. One died from HBV-cirrhosis and two were retransplanted. In the others, the last histology showed cirrhosis (three), chronic hepatitis (nine), acute hepatitis (one), and non-specific change (four patients)., Conclusions: The prevalence of de novo HBV infection in liver transplant patients was 3.5%; the aetiology was determined in 16/20 patients: from the donor in eight, and from the recipient in eight. One should be cautious when donors or recipients are anti-HBc or both anti-HBs and anti-HBc positive.

Background/aims: Orthotopic liver transplantation is currently considered as the treatment of choice for primary biliary cirrhosis in the terminal stage and, as for other autoimmune liver disease, the risk of recurrence of the disease within the graft has been raised. There is, however, some discrepancy about the risk of recurrence based on pathological analysis. In addition, pathological recurrence of primary biliary cirrhosis within the graft is not always associated with a rise in the serological markers of the disease. In order to clarify this situation, we have monitored antimitochondrial antibodies before and after transplantation., Methods: Antimitochondrial antibodies were detected by indirect immunofluorescence (variation in antibody titers) and the antimitochondrial antibodies-2 by western blotting (variation in the number of peptides recognized in 16 primary biliary cirrhosis patients followed for at least 4 years after transplantation., Results: Antimitochondrial antibody titers had normalized 1 year after transplantation in seven patients, declined in seven others and remained unchanged in two. Over the 4 years of follow up, four patients demonstrated a subsequent increase in antimitochondrial antibody titers. Western blot analysis demonstrated the loss of one or more bands in seven patients during the first operative year after transplantation and in three other patients thereafter; in six patients the western blotting profile remained identical to that obtained before transplantation. The important changes generally occurred during the first year post-transplantation, without significant changes thereafter, except for three patients who demonstrated a secondary reappearance of the initially lost band. Disappearance of all bands was never observed. There was no concordance between the normalization of antimitochondrial antibody titers (indirect immunofluorescence) and the reduction in the number of peptides recognized (western blotting). Serum bilirubin and alkaline phosphatase levels had normalized by 1 year after transplantation, and remained normal thereafter. Routine liver biopsies performed on a yearly basis did not disclose any pattern suggestive of primary biliary cirrhosis recurrence., Conclusions: Antimitochondrial antibody titers decreased in primary biliary cirrhosis patients after liver transplantation, although antimitochondrial antibodies-2 never disappeared as assessed by western blotting. In the present study these features were not associated with biochemical or histological (correction of histoclogical) evidence of primary biliary cirrhosis recurrence.